It is proposed to study the occurrence of immunosuppression at the level of the committed immune stem cell in humans and animal models with cancer. Stem-cell competance will be tested by measuring T-lymphocyte colony formation in soft agar. The adherent immune-cell populations will be isolated and tested for their ability to promote or inhibit T-cell colony formation. A correlation of inhibited T-cell colony formation and adherent cell production of prostaglandins will be sought by following prostaglandin synthesis by radioimmunoassay and labeled precursor conversion. More detailed examination of the adherent cell population from the spleen, bone, and peritoneum of animals bearing experimental cancers will be carried out. The ability of the latter cell population to synthesize prostaglandins and inhibit soft agar colony proliferation of committed T-cell will be studied. Recent evidence indicates that suppressed immune cell function, measured by in vivo as well as in vitro tests, can routinely be demonstrated in the cancer bearing host. Clinical studies in cancer patients have demonstrated the worst prognosis to be associated with immune cell depletion. It is suggested in this proposal that prostaglandins may be one of the principal effector agents of the immunosuppression seen in the cancer bearing host. Preliminary data has demonstrated an association of hyperprostaglandinemia and cancer. Additional data from in vitro studies is presented identifying prostaglandin E as the naturally occurring inhibitor of proliferation and differentiation of the committed macrophage granulocyte precursor cell as well as the T and B lymphocyte. It is hoped that this study will document that prostaglandins are important mediators of cancer immunosuppression through their inhibition of stem cell proliferation and differentiation. The information derived from such experiments could permit more rational selection of immunoactive agents for immunoadjuvant therapy protocols.